1. Hypoadrenocorticism frequently results in critical hypotension, hypovolaemia, hyponatraemia and hyperkalaemia. Perhaps even more important, hypoadrenocorticoid humans experience decreased vasoconstriction in response to exogenous administration of vasoconstrictors, such as noradrenaline. 2. We studied chronically adrenalectomized adult sheep to test the hypothesis that the reduction in pressor responsiveness is the result of increased production of nitric oxide (NO) during hypoadrenocorticism. 3. Withdrawal of steroid replacement resulted in reduced blood pressure, reduced pressor responsiveness, as well as hyperkalaemia and hyponatraemia. 4. Inhibition of NO production by NG-nitro-L-arginine methyl ester in the hypoadrenocorticoid ewes restored mean arterial pressure and pressor responsiveness response to normal values. 5. The results of these experiments support the hypothesis that reduced pressor responsiveness in the hypoadrenocorticoid state is mediated by the overproduction of NO.